A new naturally occurring GABAA receptor subunit partnership with high sensitivity to ethanol

According to the rules of GABA(A) receptor (GABA(A)R) subunit assembly, alpha 4 and alpha 6 subunits are considered to be the natural partners of delta subunits. These GABA(A)Rs are a preferred target of low, sobriety-impairing concentrations of ethanol. Here we demonstrate a new naturally occurring GABAAR subunit partnership: d subunits of hippocampal interneurons are coexpressed and colocalized with alpha 1 subunits, but not with alpha 4, alpha 6 or any other alpha subunits. Ethanol potentiates the tonic inhibition mediated by such native alpha 1/delta GABA(A)Rs in wild-type and in alpha 4 subunit-deficient (Gabra4(-/-)) mice, but not in delta subunit - deficient (Gabrd(-/-)) mice. We also ruled out any compensatory upregulation of alpha 6 subunits that might have accounted for the ethanol effect in Gabra4(-/-) mice. Thus, alpha 1/delta subunit assemblies represent a new neuronal GABA(A)R subunit partnership present in hippocampal interneurons, mediate tonic inhibitory currents and are highly sensitive to low concentrations of ethanol.